Abstract We propose to examine plasma beta amyloid (AB) levels in a subsample of 140 participants at baseline, 6, and 18 months, to preliminarily test whether exercise and mindfulness reduce and delay amyloid deposition and thus the risk for Alzheimer?s disease (AD). We will leverage the ?Remediating age-related cognitive decline: Mindfulness Based Stress Reduction and Exercise? (MEDEX) study currently funded by National Institute on Aging. MEDEX is randomizing 580 older adults with cognitive decline to receive mindfulness-based stress reduction (MBSR), MBSR plus exercise, exercise alone or health education. There has not previously been an accurate assay to detect peripheral AB differences attributable to amyloid deposition in the brain. In contrast, cerebrospinal fluid (CSF) beta amyloid 42 (AB42) has consistently shown a strong correlation with insoluble amyloid deposition as measured by PET Pittsburgh compound B (PiB) ? the AB42 level is decreased in CSF, allowing it to serve as a diagnostic test. Dr. Randy Bateman?s lab has advanced plasma AB measurement to highly precise measures (%CV 1- 2% within sample run) for AB 42, 40, and 38. They have demonstrated highly significant difference in AB concentrations and metabolism in the blood of patients with brain AB amyloidosis compared to controls. These findings have now been confirmed in three case-control studies of older adults with or without amyloid PET positivity, and by an independent group. This is a significant advance in the technique of blood AB measurement of CNS amyloid, with advanced mass spectroscopy (MS) techniques 100-fold more sensitive and 50,000x more specific than prior studies. Moreover, the longitudinal assessment of amyloid in blood reveals the potential of the blood test to track disease progression over time, thus allowing us to measure the effects of interventions that putatively slow or prevent amyloid deposition and in doing so reduce the risk of incident AD. Ours would be the first study, to our knowledge, to apply this technique in a systematic manner to the study of exercise, or mindfulness training, which are both promising and widely available interventions that could potentially reduce the risk of AD.